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Tyrosinase, the rate-limiting enzyme for melanin synthesis, is induced after ultraviolet irradiation as part of the tanning response, the major recognized photoprotective response of human skin. Other DNA-damaging agents and DNA fragments such as thymidine dinucleotides also induce tyrosinase gene expression. Moreover, like ultraviolet light they also activate p53. To determine whether p53 activation is required for this increased tyrosinase expression, we employed two experimental systems: (i) a human melanoma line (WM35) known to express wild-type p53 versus WM35 cells engineered to express a transcriptionally inactive dominant-negative p53 (WM35-p53^DN) or the empty vector alone (WM35-pCMV7) and (ii) mice with wild-type p53 versus p53 knockout mice. In WM35-p53^DN cells, the baseline p53 protein level was higher than in WM35 or WM35-pCMV7 cells, and tyrosinase transcripts were lower …